Analysis of Agonist and Antagonist Effects on Thyroid Hormone Receptor Conformation by Hydrogen/Deuterium Exchange

Thyroid hormone receptors (TRs) are ligand-gated transcription factors with critical roles in development and metabolism. Although x-ray structures of TR ligand-binding domains (LBDs) with agonists are available, comparable structures without ligand (apo-TR) or with antagonists are not. It remains important to understand apo-LBD conformation and the way that it rearranges with ligands to develop better TR pharmaceuticals. In this study, we conducted hydrogen/deuterium exchange on TR LBDs with or without agonist (T(3)) or antagonist (NH(3)). Both ligands reduce deuterium incorporation into LBD amide hydrogens, implying tighter overall folding of the domain. As predicted, mass spectroscopic analysis of individual proteolytic peptides after hydrogen/deuterium exchange reveals that ligand increases the degree of solvent protection of regions close to the buried ligand-binding pocket. However, there is also extensive ligand protection of other regions, including the dimer surface at H10-H11, providing evidence for allosteric communication between the ligand-binding pocket and distant interaction surfaces. Surprisingly, C-terminal activation helix H12, which is known to alter position with ligand, remains relatively protected from solvent in all conditions suggesting that it is packed against the LBD irrespective of the presence or type of ligand. T(3), but not NH(3), increases accessibility of the upper part of H3-H5 to solvent, and we propose that TR H12 interacts with this region in apo-TR and that this interaction is blocked by T(3) but not NH(3.) We present data from site-directed mutagenesis experiments and molecular dynamics simulations that lend support to this structural model of apo-TR and its ligand-dependent conformational changes. (Molecular Endocrinology 25: 15-31, 2011)

Erbium and Ytterbium Codoped Titanoniobophosphate Glasses for Ion-Exchange-Based Planar Waveguides

This work presents the optical properties of erbium-doped and erbium/ytterbium codoped Na(2)O-Al(2)O(3)-TiO(2)-Nb(2)O(5)-P(2)O(5) glass systems and also the characterization of planar waveguides obtained by typical thermally assisted Ag+<-> Na+ ion-exchange process. The glass systems allow the preparation of single mode and multimode planar waveguides presenting a strong and relatively broad emission at 1536 nm. The emission signal in the infrared region is intensified for silver-containing samples when compared with free-silver samples. The emission signal intensification may be attributed to a nonplasmonic energy transfer from silver species to Er3+ ions as no bands related to surface plasmon resonance (SPR) of silver nanoparticles were observed.

A new approach to organomanganese compounds: the tellurium/manganese exchange reaction

Diorganomanganese compounds react with aryl, vinyl, and alkynyl tellurides in a tellurium/manganese exchange reaction. The new mixed organomanganese reagents react selectively with electrophiles. (C) 2010 Published by Elsevier Ltd.

Solvatochromism in Binary Mixtures: First Report on a Solvation Free Energy Relationship between Solvent Exchange Equilibrium Constants and the Properties of the Medium

We have employed UV-vis spectroscopy in order to investigate details of the solvation of six solvatochromic indicators, hereafter designated as ""probes"", namely, 2,6-diphenyl-4-(2,4,6-triphenylpyridinium-1-yl) phenolate (RB); 4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePM; 1-methylquinolinium-8-olate, QB; 2-bromo-4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePMBr, 2,6-dichloro-4-(2,4,6-triphenylpyridinium-1-yl) phenolate (WB); and 2,6-dibromo-4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePMBr,, respectively. These can be divided into three pairs, each includes two probes of similar pK(a) in water and different lipophilicity. Solvation has been studied in binary mixtures, BMs, of water, W, with 12 protic organic solvents, S, including mono- and bifunctional alcohols (2-alkoxyethanoles, unsaturated and chlorinated alcohols). Each medium was treated as a mixture of S, W, and a complex solvent, S-W, formed by hydrogen bonding. Values of lambda(max) (of the probe intramolecular charge transfer) were converted into empirical polarity scales, E(T)(probe) in kcal/mol, whose values were correlated with the effective mole fraction of water in the medium, chi w(effective). This correlation furnished three equilibrium constants for the exchange of solvents in the probe solvation shell; phi(W/S) (W substitutes S): phi(S-W/W) (S-W substitutes W), and phi(S-W/S) (S-W substitutes S), respectively. The values of these constants depend on the physicochemical properties of the probe and the medium. We tested, for the first time, the applicability of a new solvation free energy relationship: phi = constant + a alpha(BM) + b beta(BM) + s(pi*(BM) + d delta) + p log P(BM), where a, b, s, and p are regression coefficients alpha(BM), beta(BM), and pi*(BM) are solvatochromic parameters of the BM, delta is a correction term for pi*, and log P is an empirical scale of lipophilicity. Correlations were carried out with two-, three-, and four-medium descriptors. In all cases, three descriptors gave satisfactory correlations; use of four parameters gave only a marginal increase of the goodness of fit. For phi(W/S), the most important descriptor was found to be the lipophilicity of the medium; for phi(S-W/W) and phi(S-W/S), solvent basicity is either statistically relevant or is the most important descriptor. These responses are different from those of E(T)(probe) of many solvatochromic indicators in pure solvents, where the importance of solvent basicity is usually marginal, and can be neglected.

Functional Expression of Chemoreceptors with the Help of a Guanine Nucleotide Exchange Factor

Odorant receptors and other chemoreceptors are usually poorly expressed in the plasma membrane of heterologous cells. A key point of regulation in G protein-mediated signaling is the interconversion between the active GTP-bound and inactive GDP-bound states of the G alpha subunit, which regulatory proteins, such as guanine nucleotide exchange factors (GEFs), can control. GEFs stimulate formation of the GTP-bound state of G alpha and therefore are considered to work as positive regulators of G protein-coupled receptor signaling. Ric-8B, a GEF that is specifically expressed in olfactory sensory neurons, promotes functional expression of odorant receptors in HEK293T cells because it amplifies the initially low receptor signaling through G alpha olf. This same strategy could be used to functionally express other types of chemoreceptors.

Rapid and direct determination of glyphosate and aminomethylphosphonic acid in water using anion-exchange chromatography with coulometric detection

A simple, rapid, and low-cost coulometric method for direct detection of glyphosate and aminomethylphosphonic acid (AMPA) in water samples using anion-exchange chromatography and coulometric detection with copper electrode is presented. Under optimized conditions, the limits of detection (LODs) (S/N = 3) were 0.038 mu g ml(-1) for glyphosate and 0.24 mu g ml(-1) for AMPA, without any preconcentration method. The calibration curves were linear and presented an excellent correlation coefficient. The method was successfully applied to the determination of glyphosate and AMPA in water samples without any kind of extraction, clean-up, or preconcentration step. No interferent was found in the water, like this, the recovery was, practically, 100%. (c) 2008 Elsevier B.V. All rights reserved.

Potential oscillations in a proton exchange membrane fuel cell with a Pd-Pt/C anode

We report in this paper the occurrence of potential oscillations in a proton exchange membrane fuel cell (PEMFC) with a Pd-Pt/C anode, fed with H(2)/100 ppm CO, and operated at 30 degrees C. We demonstrate that the use of Pd-Pt/C anode enables the emergence of dynamic instabilities in a PEMFC. Oscillations are characterized by the presence of very high oscillation amplitude, ca. 0.8 V. which is almost twice that observed in a PEMFC with a Pt-Ru/C anode under similar conditions. The effects of the H(2)/CO flow rate and cell current density on the oscillatory dynamics were investigated and the mechanism rationalized in terms of the CO oxidation and adsorption processes. We also discuss the fundamental aspects concerning the operation of a PEMFC under oscillatory regime in terms of the benefit resulting from the higher average power output. (c) 2010 Elsevier B.V. All rights reserved.

Trade effects of exchange rate fluctuations: Evidence from Sweden

An overview of the theoretical literature for the last two decades suggests that there is no clear-cut relationship one can pin down between exchange rate volatility and trade flows. Analytical results are based on specific assumptions and only hold in certain cases. Especially, the impact of exchange rate volatility on export and import activity investigated separately leads also to dissimilar conclusions among countries studied. The general presumption is that an increase in exchange rate volatility will have an adverse effect on trade flows and consequently, the overall heath of the world economy. However, neither theoretical models nor empirical studies provide us with a definitive answer, leaving obtained results highly ambiguous and inconsistent (Baum and Caglayan, 2006). We purposed to empirically investigate trade effects of exchange rate fluctuations in Sweden from the perspective of export and import in this research. The data comprises period from January 1993 to December 2006, where export and import volumes are considered from the point of their determinants, including exchange rate volatility, which has been measured through EGARCH model. The results for the case of Sweden show that short run dynamics of volatility negatively associated with both export and import, whereas considered from the case of previous period volatility it exhibits positive relationship. These results are consistent with the most findings of prior studies, where the relationship remained ambiguous.

Investigation of Iron (III) desferrioxamine B oxalate ligand exchange by UV-vis spectroscopy: the next step in developing a quantitative analytical method for measuring bioavailable iron in marine ecosystems

To date there are no analytical techniques designed to exclusively measure bioavailable iron in marine environments. The goal of this research is to develop such a technique by isolating the bioavailable iron using the terrestrial siderophore desferrioxamine B (DFB). This project contained many challenging aspects, but the specific goal of this study was to develop a robust analytical technique for quantification of Fe(III)-DFB complexes at nanomolar concentrations. Past work showed that oxalate (Ox) promotes photodissociation of Fe(III)-DFB to Fe(Il), and we are specifically interested in the mechanism of this process. A model was developed using known thermodynamic constants for Fe(III)-DFB and Fe(III) oxalato complexes and adjusting for ionic strength. The model was confirmed by monitoring the UV-VIS absorbance of the system at a variety of oxalate concentrations and pH. The model did not include ternary complexes. Next., the rate of Fe(1I) production during UV irradiation was examined. The results showed that the rate of Fe(II) production was based entirely on the [Fe(Ox)?]3- speciation, and that reoxidation of Fe(II) occurred via reactive oxygen intermediates. This reoxidation could be avoided by either decreasing the oxygen concentration or by adding a Fe(II) stabilizing reagent, such as ferrozine. Further studies need to be done to confirm that these results apply at sub nanomolar concentrations, and the issue of Fe(II) reoxidation at lower Fe concentrations needs to be addressed.

Are price limits on futures markets that cool? evidence from the brazilian merchantile & futures exchange

This paper investigates the impact of price limits on the Brazil- ian future markets using high frequency data. The aim is to identify whether there is a cool-off or a magnet effect. For that purpose, we examine a tick-by-tick data set that includes all contracts on the São Paulo stock index futures traded on the Brazilian Mercantile and Futures Exchange from January 1997 to December 1999. Our main finding is that price limits drive back prices as they approach the lower limit. There is a strong cool-off effect of the lower limit on the conditional mean, whereas the upper limit seems to entail a weak magnet effect on the conditional variance. We then build a trading strategy that accounts for the cool-off effect so as to demonstrate that the latter has not only statistical, but also economic signifi- cance. The resulting Sharpe ratio indeed is way superior to the buy-and-hold benchmarks we consider.

The trasition from fixed to floating exchange rate regimes: the case of Brazil

This dissertation evaluates macroeconomic management in Brazil from 1994 to the present, with particular focus on exchange rate policy. It points out that while Brazil's Real Plan succeeded in halting the hyperinflation that had reached more than 2000 percent in 1993, it also caused significant real appreciation of the exchange rate situation that was only made worse by the extremely high interest rates and ensuing bout of severe financial crises in the intemational arena. By the end of 1998, the accumulation of internai and externai imbalances led the authorities to drop foreign exchange controls and allow the currency to float. In spite of some initial scepticism, the flexible rate regime cum inflation target proved to work well. Inflation was kept under control; the current account position improved significantly, real interest rates fell and GDP growth resumed. Thus, while great challenges still lie ahead, the recent successes bestow some optimism on the well functioning of this exchange rate regime. The Brazilian case suggests that successful transition from one foreign exchange system to another, particularly during financial crisis, does not depend only on one variable be it fiscal or monetary. In reality, it depends on whole set of co-ordinated policies aimed at resuming price stability with as little exchange rate and output volatility as possible.

Debt composition and exchange rate balance sheet effects in Brazil: A firm level analysis

In this paper we study the interaction between macroeconomic environment and firms’ balance sheet effects in Brazil during the 1990’s. We start by assessing the influence of macroeconomic conditions on firms’ debt composition in Brazil. We found that larger firms tend to change debt currency composition more in response to a change in the exchange rate risk than small firms. We then proceed to investigate if and how exchange rate balance sheet effects affected the firms’ investment decisions. We test directly the exchange rate balance sheet effect on investment. Contrary to earlier findings (Bleakley and Cowan, 2002), we found that firms more indebted in foreign currency tend to invest less when there is an exchange rate devaluation. We tried different controls for the competitiveness effect. First, we control directly for the effect of the exchange rate on exports and imported inputs. We then pursue an alternative investigation strategy, inspired by the credit channel literature. According to this perspective, Tobin’s q can provide an adequate control for the competitiveness effect on investment. Our results provide supporting evidence for imperfect capital markets, and for a negative exchange rate balance sheet effect in Brazil. The results concerning the exchange rate balance sheet effect on investment are statistically significant and robust across the different specifications. We tested the results across different periods, classified according to the macroeconomic environment. Our findings suggest that the negative exchange rate balance sheet effect we found in the whole sample is due to the floating exchange rate period. We also found that exchange rate devaluations have important negative impact on both cash flows and sales of indebted firms. Furthermore, the impact of exchange rate variations is asymmetric, and the significant effect detected when no asymmetry is imposed is engendered by exchange rate devaluations.